The selective agonist of β3-adrenergic receptor mirabegron (MBG), clinically used to treat overactive bladders, exerts beneficial effects in animal models of colitis. Here, we aimed to enhance the therapeutic activity and safety of MBG as an anticolitic drug by implementing colon-targeted drug delivery using a prodrug approach. MBG was azo-linked with salicylic acid (SA) to yield SA-conjugated MBG (MAS), which was conjugated with aspartic acid (Asp) and glutamic acid (Glu) to yield more hydrophilic derivatives: Asp-conjugated MAS (MAS-Asp) and Glu-conjugated MAS (MAS-Glu). MBG derivatives reduced the distribution coefficient and cell permeability of MBG, which were greater with the amino acid-conjugated MAS than with MAS. MBG derivatives were cleaved to release MBG in the cecal contents. Upon oral gavage, compared with MBG, MBG derivatives delivered greater amounts of MBG to the cecum while limiting the systemic absorption of MBG, and the amino acid-conjugated MAS exhibited a greater performance than MAS. In a rat colitis model, MBG derivatives were more effective than MBG in ameliorating colonic damage and inflammation, and the amino acid-conjugated MAS was more potent than MAS. MAS-Glu was therapeutically superior to sulfasalazine, a current drug to treat inflammatory bowel disease, against rat colitis. Moreover, MBG activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-hemeoxygenase (HO)-1 pathway in inflamed colonic tissue, and the MAS-Glu-mediated amelioration of colitis was significantly compromised by an HO-1 inhibitor. Taken together, colon-targeted delivery of MBG may enhance the anticolitic activity, reduce the risk of systemic side effects of MBG, and elicit the therapeutic effects, at least partly by activating the Nrf2-HO-1 pathway.

Inflammatory bowel disease (IBD) is a multifactorial illness with a climbing prevalence worldwide. While biologics are commonly prescribed especially for severe cases, they may worsen patients' outcomes due to financial burden. Consequently, there has been an increased focus on biosimilars to improve overall disease outcomes by maintaining similar efficacy and safety while minimizing the cost of therapy. Infliximab-dyyb was the first biosimilar approved by US-FDA for IBD. Since that, the US-FDA approved 14 biosimilars with different mechanisms of action and different routes of administration for IBD patients (four infliximab biosimilars, nine adalimumab biosimilars, and most recently one ustekinumab biosimilar). It should be noted that more biologics are in the pipeline as golimumab and natalizumab patents are set to expire in the near future, and biosimilars are now in pre-clinical to phase 3 trials. Different studies have evaluated biologics' effectiveness and safety and concluded that the majority of available biosimilars are efficacious and have similar adverse effect profiles compared to their reference biologics. It is worth mentioningthat post-marketing surveillance reports revealed some risks associated with biosimilars which should be taken into consideration in future research and clinical trials to avoid health hazards. Most biologics and biosimilars are administered parenterally which results in several drawbacks such as raised risk of infections, hypersensitivity, autoimmunity, development of malignancies, liver toxicity as well as worsening of heart failure. Several drug delivery systems based on passive and active targeting mechanisms are under active investigation to overcome these limitations. This review sheds light on the emergence of biologics and biosimilars as alternatives in IBD management, the differences between them, challenges and risks, and future perspectives in IBD therapy and new trends in drug delivery systems.

Inflammatory bowel disease (IBD) refers to a group of chronic, recurrent intestinal inflammatory conditions with a complex cause and unclear underlying mechanisms. It includes two main types: Ulcerative colitis (UC) and Crohn's disease (CD). The conventional treatment of IBD mainly includes 5-aminosalicylates, glucocorticoids, and immunosuppressive drugs, which have their limitations. Recent advancements in IBD research have expanded treatment options, with biological agents playing a key role. Anti-tumor necrosis factor alpha has emerged as the first-line therapy for moderate to severe IBD. Anti-integrin antibodies have also become important for the treatment, and vedolizumab is often used in cases of anti-tumor necrosis factor-alpha failure and intolerance to other treatments. Other biological agents are being tested in clinical trials at different stages. This article reviews the efficacy and safety of the primary biological therapies for IBD and provides a comprehensive analysis of the current clinical challenges associated with the disease.

Over the last decade, the treatment options for inflammatory bowel disease (IBD) have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation. Adalimumab (ADA) is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD. In April 2021, the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira® to ADA biosimilars. Biosimilars offer a potential cost-effective, safe, and efficacious alternative to the originator, yet there remains limited real-world evidence on long-term outcomes of ADA non-medical switching in IBD.

To assess the long-term outcomes of non-medical switching from the ADA originator Humira® to an ADA biosimilar among IBD patients.

A retrospective observational chart review study was conducted on IBD patients eligible for the provincially mandated non-medical switch to an ADA biosimilar. The primary outcome was treatment persistence at 30 months post-switch. Secondary outcomes included the proportion of and reasons for therapy alteration or ADA discontinuation, loss of response (LOR) rates, adverse events (AE), and clinical and biochemical remission status. Patients who remained on the originator throughout the switch period, through compassionate support or private pay, constituted the comparison group.

Patients in the originator (n = 43) and biosimilar switch (n = 228) groups displayed similar demographics and baseline disease characteristics. By the study endpoint of 30 months, there was no difference in the rate of treatment persistence in either group (n = 36, 83.7% originator group vs n = 201, 88.2% biosimilar group, P = 0.451). Treatment persistence demonstrated similar rates of discontinuation between both study groups (log-rank P = 0.543). There was a numerical but not statistically significant difference in rates of adverse outcomes between either group (39.5% originator vs 28.9% biosimilars, P = 0.206). This included comparable rates of LOR (27.9% vs 17.5%) or AE (11.6% vs 11.4%) between the originator and biosimilar cohorts, respectively. C-reactive protein and fecal calprotectin levels were similar one year pre- and post-switch.

These data support the long-term efficacy and safety of non-medical ADA switching in IBD and will help inform patients and physicians in jurisdictions currently undergoing biosimilar switching.

The aim of this review is to explore the potential of new regenerative medicine approaches in the treatment of cholestatic liver fibrosis. Cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and biliary atresia (BA), due to the accumulation of bile, often progress to liver fibrosis, cirrhosis, and liver failure. When the disease becomes severe enough to require liver transplantation. Deeply understanding the disease's progression and fibrosis formation is crucial for better diagnosis and treatment. Current liver fibrosis treatments mainly target the root causes and no direct treatment method in fibrosis itself. Recent advances in regenerative medicine offer a potential approach that may help find the ways to target fibrosis directly, offering hope for improved outcomes. We also summarize, analyze, and discuss the current state and benefits of regenerative medicine therapies such as mesenchymal stem cell (MSC) therapy, induced pluripotent stem cells (iPSCs), and organoid technology, which may help the treatment of cholestatic liver diseases. Focusing on the latest research may reveal new targets and enhance therapeutic efficacy, potentially leading to more effective management and even curative strategies for cholestatic liver diseases.

Biologicals targeting interleukin (IL)-17 and IL-23 improve quality of life in psoriasis and other chronic autoimmune disorders with a favorable safety profile. However, current guidelines do not recommend their use in patients with recent oncologic history due to limited evidence.

To understand the impact of IL-17 and IL-23 inhibitors on cancer development, progression, and recurrence by systematically reviewing available literature.

We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Most studies investigating the use of IL-23 and IL-17 blockers did not find a higher incidence of cancer compared to the general population. One study observed no relapse in patients with a history of cancer.

The systematic review is limited due to variations in study designs and outcomes, making it difficult to achieve a comprehensive synthesis and comparison between studies. Furthermore, small sample sizes were notable.

Preclinical studies suggest that treating psoriasis with IL-17 or IL-23 blockers is safe, also in patients witch active cancer or a history of it. Pharmacovigilance data show no increased malignancy rate in patients treated with these treatment modalities. However, data on relapse in patients with a history or active malignancy are limited.

Biologics are important therapeutic agents for pediatric Crohn's disease. Discontinuation of biologics is known to increase the relapse rate up to 71.4% in these patients; however, their long-term use increases the risk of opportunistic infections and causes economic burden and psychological fatigue. Therefore, taking a drug holiday is meaningful, even if the biologics cannot be completely discontinued. This study aimed to analyze the risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease.

We retrospectively reviewed the data of 435 children with Crohn's disease who visited a single health center between March 2013 and March 2021. Subsequently, we analyzed data from the patients who discontinued biologics after deep remission.

Among the enrolled patients, 388 were followed up for ≥2 years, and of these, 357 were administered biologics. A total of 103 patients discontinued biologics after deep remission, subsequently 31 maintained remission and 72 relapsed. The shorter the duration of biologic treatment (odds ratio of 0.444, P = 0.029), the higher the ESR (odds ratio of 1.294, P = 0.009) and fecal calprotectin (odds ratio of 1.010, P = 0.032), and the less histological remission at the time of discontinuation of biologics (odds ratio of 0.119, P = 0.026), the greater the risk of relapse after discontinuation of biologics.

We identified factors associated with relapse after discontinuation of biologics. The results suggest that biologics can be discontinued in the absence of these factors after deep remission. However, because the relapse rate may increase after the discontinuation of biologics, close monitoring is important, and if necessary, re-administration of biologics should be actively considered.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is characterized by persistent and recurrent gastrointestinal inflammation. Conventional IBD therapies often involve the use of antibiotics, NSAIDs, biological agents, and immunomodulators. While these medications can mitigate acute inflammatory symptoms, their long-term efficacy is frequently compromised due to cumulative toxic effects. In recent years, significant attention has shifted toward nanoparticle (NP)-based therapies as potential alternatives for IBD management. Various drug delivery strategies, including those targeting microbiota interactions, ligand-receptor binding, pH sensitivity, biodegradability, pressure response, and specific charge and size parameters, have been explored and optimized in animal studies. This review provides a comprehensive overview of the current landscape of chitosan NP-mediated drug delivery systems for IBD treatment. Additionally, it will discuss the prevailing challenges and propose future research directions to advance chitosan NP-based therapeutic strategies for IBD.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field.

Small molecules, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor modulators (S1PRMs), are promising new treatments for inflammatory bowel disease (IBD). Small molecules exhibit more predictable pharmacokinetics than biologics, are less likely to induce immune responses, and can be administered orally. JAK inhibitors function by blocking the activity of JAK enzymes, which prevents the subsequent phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins. Tofacitinib and filgotinib are approved for treating ulcerative colitis (UC), while upadacitinib is approved for UC and Crohn's disease. Nevertheless, JAK inhibitors can increase the risk of herpes zoster, cancer, major adverse cardiovascular events, and venous thromboembolism. S1PRMs bind to S1PRs, particularly S1PR1, on lymphocytes. This interaction inhibits lymphocytes from exiting the lymph nodes and migrating to the gut, thereby reducing inflammation and the immune response in the intestinal mucosa. Ozanimod and etrasimod are S1PRMs approved for the treatment of UC, but they can cause side effects such as bradycardia, conduction disorder, and macular edema. Overall, JAK inhibitors and S1PRMs offer significant benefits in managing IBD, although their potential side effects require careful monitoring.

Inflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US).

Mortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality.

Age-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08).

Disparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.

Cannabis use is common in inflammatory bowel disease (IBD). Recent studies demonstrated that use of cannabis may relieve symptoms; however, it is still unclear how safe cannabis and its derivatives are for IBD patients. We performed this study to evaluate the impact of cannabis use on several key clinical outcomes in IBD.

We performed a retrospective study using the TriNetX Diamond Network. Cannabis use and noncannabis use subcohorts were identified for 3 patient groups: (1) IBD, (2) Crohn's disease (CD), and (3) ulcerative colitis (UC). Baseline differences between subcohorts for each group were controlled by propensity score matching. In each group, we compared relative incidence of emergency department (ED) visits, hospitalization, corticosteroid use, opioid use, IBD-related surgery, and death between cannabis users and noncannabis users.

Inflammatory bowel disease cannabis users demonstrated an increased risk for corticosteroid use (risk ratios [R],1.095; 95% CI, 1.021-1.174; P = .011), ED visits (RR, 2.143; 95% CI, 2.034-2.257; P < .001), hospitalizations (RR, 1.925; 95% CI, 1.783-2.079; P < .001) and opioid use (RR, 1.35; 95% CI, 1.14-1.6); P < .001), but not an increased risk of IBD-related surgery or death. The CD and UC groups exhibited similar outcomes, except only CD demonstrated an increased risk for corticosteroid and opioid use.

Cannabis use in IBD patients is associated with several poor clinical outcomes, including increased risk of corticosteroid and opioid use, ED visits and hospitalization, though not IBD-related surgery or death. It is not clear what drives these risks or whether they are directly related to IBD-associated disease activity or other factors. Further prospective studies are warranted to more carefully investigate these relationships.

Biologics, a mainstay in inflammatory bowel disease (IBD) treatment, typically require prior authorization from insurance companies. Multiple studies show that African Americans are less likely to be prescribed biologics. The prior authorization process may perpetuate disparities in healthcare. This study evaluated the approval time for biologics in IBD.

A chart review of IBD patients seen in a university gastroenterology clinic over 5 years was performed. Patient gender, race, IBD subtype, biologic use, and insurance type were recorded. Insurance type was classified as private or public (Medicaid or Medicare). Biologic agents evaluated included infliximab, adalimumab, vedolizumab and ustekinumab. Length of time to approval (TTA) and length of time to first infusion or administration (TFI) were recorded. Analysis was performed using t-testing, Fisher's exact testing, and ANOVA with significance set at p<0.05. The study was IRB approved.

458 charts were analyzed. 66 patients were being treated with a biologic. 42 had private insurance, 16 Medicaid and 8 Medicare. 37 patients had ulcerative colitis, 27 Crohn's disease, and 2 indeterminate colitis. There were 38 men and 28 women. 32 patients were white, 26 African American, 1 Asian, 5 other, and 2 declined identification. Average TTA was 30.5 days (range 1-145) and average TFI was 45.3 days (range 2-166). African Americans were more often on public insurance compared to whites (p=0.0001). Crohn's disease compared to ulcerative colitis patients were more often on public insurance (p=0.017). Significantly more private compared to public insurance patients were on infliximab (p=0.001). Medicaid and Medicare patients had significantly longer mean TTAs than private insurance patients (49.1 and 52.7 vs 19.4 days, p=0.007). African Americans had significantly longer mean TTA compared to whites (45.9 vs 24.8 days, p=0.044). Crohn's disease compared to ulcerative colitis patients had significantly longer mean TTA (39.7 vs 21.8 days, p=0.050).

This study shows that prior authorization for biologic therapy was longer for African Americans. Patients on public insurance also tend to have a longer TTA, and more African Americans were on public insurance compared to White patients in this study which may explain the difference in biologic access for African Americans.

This analysis estimated the number of inflammatory bowel disease (IBD) patients presenting criteria of eligibility for biological therapies in an Italian real-world setting.

An observational analysis was performed on administrative databases of a sample of Local Health Units, covering 11.3% of the national population. Adult IBD patients (CD or UC) from 2010 to the end of data availability were included. Eligibility criteria for biologics were the following: Criterion A, steroid-refractory active disease; Criterion B, steroid-dependent patients; Criterion C, intolerance or contraindication to conventional therapies; Criterion D, severe relapsing disease; Criterion E (CD only), highly active CD disease and poor prognosis.

Of 26,781 IBD patient identified, 18,264 (68.2%) were treated: 3,125 (11.7%) with biologics and 15,139 (56.5%) non-biotreated. Among non-biotreated, 7,651 (28.6%) met at least one eligibility criterion for biologics, with criterion B (steroid-dependence) and criterion D (relapse) as the most represented (58-27% and 56-76%, respectively). Data reportioned to the Italian population estimated 67,635 patients as potentially eligible for biologics.

This real-world analysis showed a trend towards undertreatment with biologics in IBD patients with 28.6% being potentially eligible, suggesting that an unmet medical need still exists among the Italian general clinical practice for IBD management.

Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the exposure of bacterial antigens to the immune system thereby perpetuating chronic inflammation. Currently, most of the approved IBD therapies target individual pro-inflammatory cytokines and pathways. However, they fail in approximately 50% of patients due to their inability to overcome the redundant pro inflammatory immune responses. There is increasing interest in the therapeutic potential of T regulatory cells (Tregs) in inflammatory conditions due to their widespread capability to dampen inflammation, promote tolerance of intestinal bacteria, facilitate healing of the mucosal barrier and ability to be engineered for more targeted therapy. Intestinal Treg populations are inherently shaped by dietary molecules and gut microbiota-derived metabolites. Thus, understanding how these molecules influence Treg-mediated preservation of the intestinal barrier will provide insights into immune tolerance-mediated mucosal homeostasis. This review comprehensively explores the interplay between diet, gut microbiota, and immune system in influencing the intestinal barrier function to attenuate the progression of colitis.

Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α), which is present in high levels in the blood serum, mucosa and stool of people with Crohn's disease.

To evaluate the benefits and harms of infliximab alone or in combination with another agent for induction of remission in Crohn's disease compared to placebo or active medical therapies.

On 31 August 2021 and 4 March 2023, we searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and World Health Organization ICTRP.

Randomised control trials (RCTs) comparing infliximab alone or in combination with another agent to placebo or another active comparator in adults with active Crohn's disease.

Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were clinical remission, clinical response and withdrawals due to adverse events. Our secondary outcomes were endoscopic remission, histological remission, endoscopic response, and serious and total adverse events.

The search identified 10 RCTs with 1101 participants. They were conducted between 1999 and 2019, and 7/10 RCTs included biologically naive participants. All but one RCT, which did not provide information, were multicentre and funded by pharmaceutical companies, and their authors declared conflicts. The age of the participants ranged from 26 to 65 years. Results were based on one study unless otherwise stated. Infliximab 5 mg/kg to 10 mg/kg may be more effective than placebo at week four for clinical remission (30/55 versus 3/25; RR 4.55, 95% CI 1.53 to 13.50; number needed to treat for an additional beneficial outcome (NNTB) 3) and response (36/55 versus 4/25; RR 4.09, 95% CI 1.63 to 10.25, NNTB 3). The evidence was low certainty. The study did not report withdrawals due to adverse events. We could not draw conclusions on the effects of infliximab 5 mg/kg to 10 mg/kg compared to placebo for fistulating participants for clinical remission (29/63 versus 4/31; RR 3.57, 95% CI 1.38 to 9.25; NNTB 4), response (48/106 versus 15/75; RR 1.94, 95% CI 1.10 to 3.41; NNTB 6; 2 studies) or withdrawals due to adverse events (2/63 versus 0/31; RR 2.50, 95% CI 0.12 to 50.54). The evidence was very low certainty. Infliximab used in combination with purine analogues is probably more effective than purine analogues alone for clinical remission at weeks 24 to 26 (182/301 versus 95/302; RR 1.92, 95% CI 1.59 to 2.32, NNTB 4; 4 studies; moderate-certainty evidence) and clinical response at week 26 (107/177 versus 66/178; RR 1.64, 95% CI 1.31 to 2.05; NNTB 5; 2 studies; moderate-certainty evidence). There may be little or no difference in withdrawals due to adverse events at week 26 (62/302 versus 53/301; RR 0.87, 95% CI 0.63 to 1.21; 4 studies; low-certainty evidence). Infliximab alone may be more effective than purine analogues alone at week 26 for clinical remission (85/177 versus 57/178; RR 1.50, 95% CI 1.15 to 1.95; NNTB 7; 2 studies) and response (94/177 versus 66/178; RR 1.44, 95% CI 1.13 to 1.82; NNTB 7; 2 studies). There may be little or no difference in withdrawals due to adverse events (30/177 versus 43/178; RR 0.70, 95% CI 0.46 to 1.06; 4 studies). The evidence was low certainty. We could not draw any conclusions on the effects of infliximab 5 mg/kg compared to 10 mg/kg for clinical remission (19/27 versus 11/28; RR 1.79, 95% CI 1.06 to 3.02) and response (22/27 versus 24/28; RR 1.63, 95% CI 1.08 to 2.46). The evidence was very low certainty. Withdrawals due to adverse events were not reported. We could not draw any conclusions on the effects of infliximab 5 mg/kg compared to 10 mg/kg in an exclusively fistulating population for clinical remission (17/31 versus 12/32; RR 1.46, 95% CI 0.84 to 2.53), response (21/31 versus 18/32; RR 1.20, 95% CI 0.82 to 1.78), or withdrawals due to adverse events (1/31 versus 1/32; RR 1.03, 95% CI 0.07 to 15.79). The evidence was very low certainty. We could not draw any conclusions on the effects of infliximab 5 mg/kg compared to 20 mg/kg for clinical remission (19/27 versus 11/28; RR 1.79, 95% CI 1.06 to 3.02) or response (22/27 versus 18/28; RR 1.27, 95% CI 0.91 to 1.76). The evidence was very low certainty. Withdrawals due to adverse events were not reported. We could not draw any conclusions on the effects of infliximab 10 mg/kg compared to 20 mg/kg for clinical remission (11/28 versus 11/28; RR 1.00, 95% CI 0.52 to 1.92) or response (14/28 versus 18/28; RR 0.78, 95% CI 0.49 to 1.23). The evidence was very low certainty. Withdrawals due to adverse events were not reported. There may be little or no difference between infliximab and a CT-P13 biosimilar at week six for clinical remission (47/109 versus 49/111; RR 0.98, 95% CI 0.72 to 1.32), response (67/109 versus 70/111; RR 0.97, 95% CI 0.79 to 1.20) and withdrawals due to adverse events (21/109 versus 17/111; RR 1.26, 95% CI 0.70 to 2.25). The evidence was low certainty.

Infliximab in combination with purine analogues is probably more effective than purine analogues alone in inducing clinical remission and clinical response. Infliximab alone may be more effective in inducing clinical remission and response than purine analogues alone or placebo. Infliximab may be similar in efficacy to a CT-P13 biosimilar and there may be little or no difference in withdrawals due to adverse events. We were unable to draw meaningful conclusions as to whether infliximab alone is effective when used for exclusively fistulating populations. There was evidence that there may be little or no difference in withdrawal due to adverse events between infliximab plus purines compared with purines alone, as well as infliximab alone compared with purines alone. Meaningful conclusions cannot be drawn on all other outcomes related to adverse events due to very low certainty evidence.

In our previous study, riluzole azo-linked to salicylic acid (RAS) was prepared as a colon-targeted prodrug of riluzole (RLZ) to facilitate the repositioning of RLZ as an anticolitic drug. RAS is more effective against rat colitis than RLZ and sulfasalazine, currently used as an anti-inflammatory bowel disease drug. The aim of this study is to further improve colon specificity, anticolitic potency, and safety of RAS. N-succinylaspart-1-ylRLZ (SAR) and N-succinylglutam-1-ylRLZ (SGR) were synthesized and evaluated as a "me-better" colon-targeted prodrug of RLZ against rat colitis. SAR but not SGR was converted to RLZ in the cecal contents, whereas both conjugates remained intact in the small intestine. When comparing the colon specificity of SAR with that of RAS, the distribution coefficient and cell permeability of SAR were lower than those of RAS. In parallel, oral SAR delivered a greater amount of RLZ to the cecum of rats than oral RAS. In a DNBS-induced rat model of colitis, oral SAR mitigated colonic damage and inflammation and was more potent than oral RAS. Moreover, upon oral administration, SAR had a greater ability to limit the systemic absorption of RLZ than RAS, indicating a reduced risk of systemic side effects of SAR. Taken together, SAR may be a "me-better" colon-targeted prodrug of RLZ to improve the safety and anticolitic potency of RAS, an azo-type colon-targeted prodrug of RLZ.

The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients.

Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis.

In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes.

Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.

Colonic inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn's colitis (CC). Patients with IBD are at increased risk for colitis-associated colorectal cancer (CACRC) compared to the general population. CACRC is preceded by IBD, characterized by highly heterogenous, pharmacologically incurable, pertinacious, worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the duration and severity of inflammation, which is influenced by the exogenous free hemoglobin alpha chain (HbαC), a byproduct of infiltrating immune cells; extravasated erythrocytes; and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS), which is exacerbated by decreased tissue antioxidant defenses. Mitigation of the Fenton Reaction via pharmaceutical therapy would attenuate ROS, promote apoptosis and DNAD repair, and subsequently prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin's clearance rate from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Further, deferoxamine's hydrophilic structure limits its ability to cross cell membranes. Finally, the effectiveness of flavonoids, natural herb antioxidants, is associated with the high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. The molecular immunopathogenesis pathways of CACRC herein reviewed are broadly still not well understood. Therefore, this timely review outlines the molecular and immunological basis of disease pathogenesis and pharmaceutical intervention as a protective measure for CACRC.

Biologic therapies have been increasingly developed and used for the treatment of severe inflammatory diseases. However, the safety and efficacy profile of biologic drugs in patients with HIV is not well established as this patient population is historically excluded from clinical trials. We review the available evidence of biologic use in people with HIV. We conducted a systematic review of the literature up to June 29, 2022 and included studies that treated patients with HIV who have inflammatory disease using biologic drugs. Clinical data regarding safety and efficacy were abstracted into tables. One hundred twelve studies were included, and 179 patients were included in our study. Nearly all classes of biologics drugs had a favorable safety profile with minimal or minor adverse events. Anti-CD-20 inhibitors and TNF-alpha inhibitors were associated with opportunistic infections. Transient increase in HIV viral load was noted with use of some agents such as TNF-alpha inhibitors. The quality of evidence is low, restricted to case reports and retrospective reviews. However, the safety profile of biologics observed in these patients with HIV was overall favorable.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Crohn's disease (CD) and Ulcerative colitis (UC) are the two major types affecting millions across the globe. Various immunomodulatory drugs consisting of small molecules (thiopurines, methotrexate and tofacitinib) and biologics are used to treat IBD. Thiopurines (TP) are widely used in the treatment of IBD and it plays an important role both alone and in combination with anti-TNF agents as IBD maintenance therapy. Although the advent of biologics therapy has significantly advanced the management of IBD, TP remains the mainstay of treatment in resource-limited and low economic settings. However, the recently commenced pandemic has raised uncertainty over the safety of the use of immunosuppressant drugs such as TP among healthcare care providers and patients, as there is a scarcity of data on whether IBD patients are at higher risk of COVID-19 infection or more prone to its severe outcomes.

This review aims to encapsulate evidence on the risk of COVID-19 infection and its severe prognosis in IBD patients on TP. Additionally, it also evaluates the role of TP in inhibiting the viral protease, a potential drug target, essential for the replication and pathogenesis of the virus.

Emerging evidence suggests that TP therapy is safe during the current pandemic and does not carry an elevated risk when used as monotherapy or in combination with other IBD drugs. In-vitro studies demonstrate that TP is a potential therapeutic for present and future betacoronavirus pandemics.

Random mutagenesis is the natural opportunity for proteins to evolve and biotechnologically it has been exploited to create diversity and identify variants with improved characteristics in the mutant pools. Rational mutagenesis based on biophysical assumptions and supported by computational power has been proposed as a faster and more predictable strategy to reach the same aim. In this work we confirm that substantial improvements in terms of both affinity and stability of nanobodies can be obtained by using combinations of algorithms, even for binders with already high affinity and elevated thermal stability. Furthermore, in silico approaches allowed the development of an optimized bispecific construct able to bind simultaneously the two clinically relevant antigens TNF-α and IL-23 and, by means of its enhanced avidity, to inhibit effectively the apoptosis of TNF-α-sensitive L929 cells. The results revealed that salt bridges, hydrogen bonds, aromatic-aromatic and cation-pi interactions had a critical role in increasing affinity. We provided a platform for the construction of high-affinity bispecific constructs based on nanobodies that can have relevant applications for the control of all those biological mechanisms in which more than a single antigen must be targeted to increase the treatment effectiveness and avoid resistance mechanisms.

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.

BI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an 'interchangeable' biosimilar.

The aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP.

We conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2-12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14-48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration-time curve (AUCτ,30-32) and maximum observed drug plasma concentration (Cmax,30-32), measured after the third switch during the Week 30-32 dosing interval.

238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching (n = 118) or continuous arms (n = 120). Adjusted mean Cmax,30-32 was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUCτ,30-32 was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUCτ,30-32 was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for Cmax,30-32. Both CIs were within a predefined bioequivalence range of 80.0-125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period.

Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between adalimumab RP and BI 695501.

ClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20.

There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn's disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes.

This post hoc analysis included data from 220 biologic-naïve CD participants with response to induction therapy from 2 clinical trial programs. Participants achieving 1-year clinical remission (CR) (Crohn's disease activity index <150), corticosteroid-free CR, normalization of fecal calprotectin (FC), endoscopic response (Simple Endoscopic Score for CD decrease ≥50% from baseline), and endoscopic remission (ER) (Simple Endoscopic Score for CD <3) were compared. Multivariate logistic regression evaluated the likelihood of achieving the outcomes adjusted for confounders. Propensity score matching created a cohort with similar distribution of baseline covariates.

One-year CR and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15; 95% CI, 0.67-1.98; P = .681; corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58; 95% CI, 0.23-1.47; P = .251). Compared with ustekinumab-treated patients, infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59; 95% CI, 1.34-9.66; P = .011) and ER (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35; 95% CI, 1.07-10.49; P = .038). Among patients with FC ≥250 mg/kg at baseline, normalization (<250 mg/kg) at 1-year was similar between groups. Similar results were observed within the propensity matched population for all analyses.

Treatment with infliximab and ustekinumab among induction responders achieved 1-year CR with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes. Findings should be interpreted with caution as our analyses were unpowered.

The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment.

This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases.

Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1-3 months).

Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.

Comparative effectiveness has become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs ustekinumab induction therapy for moderate to severe biologic-naïve Crohn's disease (CD) using patient-level data from randomized controlled trials.

This was a post hoc analysis of 2 large CD clinical trial programs that included data on 420 biologic-naïve CD patients. Differences in proportions of patients achieving week 6 clinical remission, clinical response, and normalization of calprotectin were compared. Multivariate logistic regression was used to adjust for confounders. Sensitivity analysis was conducted using propensity scores to create a cohort of matched participants with similar distribution of baseline covariates.

At week 6, a comparable number of patients achieved clinical remission with infliximab compared with patients treated with ustekinumab (44.9% vs 37.9%; adjusted odds ratio [aOR], 1.22; 95% CI, 0.79-1.89). Similarly, at week 6 the clinical response rates were not significantly different (58.4% infliximab vs 54.9% ustekinumab; aOR, 1.25; 95% CI, 0.82-1.90). No significant difference was observed between treatment groups for achieving a week 6 fecal calprotectin level less than 250 mcg/L in those with increased values at baseline (42.3% infliximab vs 34.7% ustekinumab; aOR, 1.34; 95% CI, 0.79-2.28). Similar results were seen for all analyses performed within the propensity matched cohort.

Based on this post hoc analysis, infliximab and ustekinumab appear to have similar efficacy and speed of onset in patients with CD who are biologic-naïve.

Inflammatory bowel diseases [IBD] exhibit intestinal and systemic manifestations. Nonalcoholic fatty liver disease [NAFLD] is a common co-existing condition, possibly contributing to the cardio-metabolic burden and overall morbidity. Εmerging therapeutic choices of biologic agents have modified the clinical course of IBD; however, their impact on IBD-associated NAFLD has not been extensively evaluated. The prevalence of NAFLD varies among IBD patients, but it appears higher than in the general population in the majority of quality studies. In terms of pathogenetic and risk factors of NAFLD, they may vary with IBD activity. Dysbiosis, mucosal damage, and cytokine release have been implicated in the pathogenesis during the relapses, whereas metabolic risk factors seem to play a dominant role during the remissions of IBD. Considering biologics, although quality data are scarce, agents suppressing tumour necrosis factor may offer potential benefits in IBD-associated NAFLD, whereas anti-integrins do not appear to confer any therapeutic advantage. In conclusion, IBD-associated NAFLD possibly follows two different patterns, one manifested during the relapses and one during the remissions of IBD. Some, but not all, biologics may benefit NAFLD in patients with IBD. Further mechanistic and prospective cohort studies are warranted to illuminate the effects of various biologics on NAFLD.

The human body is a natural habitat for a multitude of microorganisms, with bacteria being the major constituent of the microbiota. These bacteria colonize discrete anatomical locations that provide suitable conditions for their survival. Many bacterial species, both symbiotic and pathogenic, interact with the host via biochemical signaling. Based on these attributes, commensal and attenuated pathogenic bacteria have been engineered to deliver therapeutic molecules to target specific diseases. Recent advances in synthetic biology have enabled us to perform complex genetic modifications in live bacteria and bacteria-derived particles, which simulate micron or submicron lipid-based vectors, for the targeted delivery of therapeutic agents. In this review, we highlight various examples of engineered bacteria or bacteria-derived particles that encapsulate, secrete, or surface-display therapeutic molecules for the treatment or prevention of various diseases. The review highlights recent studies on (i) the production of therapeutics by microbial cell factories, (ii) disease-triggered release of therapeutics by sense and respond systems, (iii) bacteria targeting tumor hypoxia, and (iv) bacteria-derived particles as chassis for drug delivery. In addition, we discuss the potential of such drug delivery systems to be translated into clinical therapies.

The increasing incidence of inflammatory bowel disease (IBD) globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions. The inception of anti-tumor necrosis factor-α (TNF-α) had resulted in a trend shift from surgical interventions. However, as the patents of approved anti-TNF-α drugs expire, biological copies of the many approved products are in the pipeline. The most commonly used biosimilar for IBD has been infliximab, followed by Adalimumab biosimilars which have been approved in major countries across the world. Although biosimilars are approved on the basis of similarity of their reference product, the lack of real-world evidence of its safety in ulcerative colitis and Crohn's disease patients has contributed to physicians' hesitancy. However, biosimilars are expected to reduce treatment costs and provide economic benefits.

Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and dysentery, infection-derived gastroenteritis. However, there is no scientific study that validates its clinical use as an anti-inflammatory in the intestine.

This study aimed to investigate the anti-inflammatory properties of the ethanolic extract of Lepidium virginicum L. (ELv) in an animal model of inflammatory bowel disease (IBD)-like colitis.

The 2,4-dinitrobenzene sulfonic acid (DNBS) animal model of IBD was used. Colitis was induced by intrarectal instillation of 200 mg/kg of DNBS dissolved vehicle, 50% ethanol. Control rats only received the vehicle. Six hours posterior to DNBS administration, ELv (3, 30, or 100 mg/kg) was administered daily by gavage or intraperitoneal injection. The onset and course of the inflammatory response were monitored by assessing weight loss, stool consistency, and fecal blood. Colonic damage was evaluated by colon weight/length ratio, histopathology, colonic myeloperoxidase (MPO) activity, and gene expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), chemokine C-X-C motif ligand 1 (CXCL-1), and interleukin-6 (IL-6).

Rats treated with DNBS displayed significant weight loss, diarrhea, fecal blood, colon shortening, a significant increase in immune cell infiltration and MPO activity, as well as increased proinflammatory cytokine expression. Intraperitoneal administration of ELv significantly reduced colon inflammation, whereas oral treatment proved to be ineffective. In fact, intraperitoneal ELv significantly attenuated the clinical manifestations of colitis, immune cell infiltration, MPO activity, and pro-inflammatory (CXCL-1, TNF-α, and IL-1β) gene expression in a dose-dependent manner.

Traditional medicine has employed ELv as a remedy for common infection-derived gastrointestinal symptoms; however, we hereby present the first published study validating its anti-inflammatory properties in the mitigation of DNBS-induced colitis.

Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population.

We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population.

We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively).

This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.

Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.^1-4 One way to investigate this treatment gap in CD is to look at the "net" remission rates in clinical trials defined as the actual percentage of patients enrolled during induction who are in remission at the end of maintenance. Indeed, most of the seminal clinical trials in CD used a "responder" methodology, where only patients who responded during induction were rerandomized to maintenance.

With many options available for treating inflammatory bowel disease (IBD) in Europe, this study sought to characterize physician treatment preferences and real-world treatment patterns in patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD).

This was a retrospective, noninterventional, physician-administered study. Gastroenterologists and general practitioners (n = 348) in France, Germany, and the United Kingdom provided information on treatment preferences and extracted information from records of patients with moderate-to-severe UC (n = 587) or CD (n = 417) who had received biologic, biosimilar or Janus kinase inhibitor therapies (2014-2019) and had IBD-related medical history available 6 months before and after treatment initiation.

Physicians largely preferred infliximab and adalimumab or their biosimilars as first-line therapy for UC (originators, 65.8%; biosimilars, 26.1%) and CD (originators, 61.8%; biosimilars, 30.5%). Effectiveness was the most cited reason for treatment preference (92%-93% of physicians). Three-quarters of patients (UC, 75.8%; CD, 73.6%) received infliximab or adalimumab originators in the first line, with more patients receiving infliximab biosimilars than adalimumab biosimilars (12.4%-12.5% and 0.5%-4.1%, respectively, across UC and CD). Persistence was longer for first-line infliximab than adalimumab (UC, 26.6 vs 21.2 months; CD, 31.2 vs 26.7 months) and was generally shorter for their respective biosimilars. Nonbiologic treatments were used in combination with biologics in 14.1% (UC) and 11.5% (CD) of patients. Most patients received 1 biologic therapy (UC, 90.6%; CD, 83.2%); only 9.4% (UC) and 16.8% (CD) received a second biologic.

Infliximab and adalimumab originators dominated first-line biologic therapy for moderate-to-severe UC and CD. Understanding real-world treatment patterns can help assess new treatment uptake and suggest opportunities for improving treatment.

Despite the effectiveness of several biological agents in the treatment of inflammatory bowel disease (IBD), some patients respond better than others. Such discrepancies are often evident early in the treatment course. The aim of this study is to identify the risks and assess the rate of early biological discontinuation (BD) among IBD patients.

In this retrospective cohort study conducted in Bahrain all IBD patients who were administered biological agents between June 2009 and June 2019 were included. Medical records were reviewed to collect study data and confirm IBD diagnoses. Early discontinuation of biological agents was defined by discontinuation of a biological agent (within 6 months from administration). Montreal classification was used to classify Crohn's disease and ulcerative colitis (UC) according to location and extension, respectively.

Ineffectiveness was the most common reason for early BD. Early BD was not related to the type of IBD, biological agent used, or to most patient-related factors (such as gender and family history). Patient age at index biological initiation was the only independent significant predictor of early BD (P = 0.045, adjusted odds ratios (95% CI): 1.06 (1.001-1.116)] even after correction of two significant factors: comorbid diabetes and marked weight loss at diagnosis.

The older the IBD patient at the time of biological therapy initiation, the higher the incidence of early BD. Therefore, caution and close follow-up are required for biological therapy among elderly patients to assess effectiveness and adverse drug reactions.

The aim of this study was to explore potential correlation of the MR imaging features and clinical characteristics with formation of perianal abscess in children with Crohn's perianal fistulas (CPF).

From 2010 to 2020, pediatric patients with CPF diagnosis on their first pelvic MRI were identified retrospectively. All patients were divided into two groups based on the presence or absence of perianal abscess. Baseline clinical and MRI characteristics were recorded for each patient. All the statistical calculations were performed using R (version 3.6.3).

A total of 60 patients [F:M 17:43, median age 14 years (IQR 10-15), ranging 3-18 years] were included in this study. Forty-four abscesses were identified in 36/60 children (mean volume 3 ± 8.6 ml, median 0.3 ml). In 24/60 patients with perianal disease, no abscess was detected on the MRI. Ten patients (28%) showed perianal abscess on pelvic MRI at the initial diagnosis. The rate of active disease on colonoscopy (visible ulcerations/aphthous ulcers) was similar in both groups (95% vs. 94%). With regards to disease location, the majority of patients (40/60, 66.6%) in both groups had ileocolonic CD. All patients without abscess had a single perianal fistula (n = 24; 3 simple and 21 complex fistulae), however, patients with perianal abscess tended to have >1 fistulous tracts (n = 50 fistulas; all complex, 27 single, 10 double and 1 triple). Intersphincteric fistula was the most common fistula type in both groups (79% and 66%, p = 0.1). The total length of fistula (3.8 ± 1.7 vs. 2.8 ± 0.8 cm, p = 0.006) and presence of multiple external openings (n = 25 vs. 7, p = 0.019) were significantly higher in patients with abscesses, and fistula length >3.3 cm showed 80% specificity and 83% PPV for the presence of perianal abscess. Fistulas were symptomatic (pain, bleeding or drainage) at similar rates in both groups (68% and 70%, p = 0.1).

Pediatric patients with CPF who develop perianal abscess have a distinct imaging phenotype defined by longer fistula length (>3.3 cm), multiple skin openings and multiple fistulous tracts (≥2) on MRI. Patients who have these features but does not have an abscess on imaging may merit more aggressive treatment (and close monitoring) to prevent the development of an abscess.

Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient.Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients.The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient's role in therapeutical decision-making and how does IBD affect the patient's work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives.The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease.